IMPORTANCE Vaccination represents our best therapeutic option against influenza viral infections. However, the efficacy of current influenza vaccines is suboptimal, and novel approaches are necessary for the prevention of disease caused by this important human respiratory pathogen. In this work, we describe a novel approach to generate safer and more efficient live attenuated influenza vaccines (LAIV) based on recombinant viruses encoding non-overlapping and independent M1/M2 (Ms) or both M1/M2 and NS1/NEP (Ms/NSs) open reading frames. Viruses containing a modified M segment were highly attenuated in mice, but able to confer, upon a single intranasal immunization, complete protection against a lethal homologous challenge with wild-type virus. Notably, protection efficacy conferred by our split M viruses was better than that obtained with the current temperature sensitive influenza LAIV. Altogether, these results open a new avenue for the development of safer and more protective LAIV based on genome reorganization of spliced viral RNA segments.